Radiation Oncology for Cure and Palliation

Chapter 1

Introduction

Robert G. Parker MD¹, Nora A. Janjan MD² and Michael T. Selch MD¹

(1)

Department of Radiation Oncology, UCLA School of Medicine, University of California, Los Angeles, 200 UCLA Medical Plaza, Suite B265, 90095–6951, Los Angeles, CA, USA

(2)

Department of Radiation Oncology, M.D. Anderson Cancer Center, 77030, 1515 Holcombe Boulevard, Houston, TX, USA

To cure sometimes to relieve often to comfort always

Attributed to Trideau

Each year in the United States, approximately 1,500,000 people will be initially diagnosed as victims of cancer [1]. Because the tumor will be extensive in many at the time of diagnosis, treatment with curative intent will be possible in only one-half of these people. In addition, treatment with curative intent will fail in as many as 50 %. Therefore, the majority of patients with cancer will require relief of the symptoms and signs caused by their disease. Objectives of palliative treatment are independent of prolongation of life, although this may be a secondary benefit. Relief of suffering and avoidance of doing harm are basic tenets of medicine [2]. Indeed patients may fear suffering more than death.

Problems requiring palliation include those that are physical (loss or alteration of body function, disfigurement, pain) and those that are psychological (fears of dying, developing pain, abandonment by physicians, family and friends, dependency, unemployment, financial disaster).

Therefore, adequate palliative management must be broad-based, starting with the diagnosis of cancer and continuing throughout the illness until the death of the patient, and requires comforting the family and friends.

Palliative management of the patient with cancer requires the coordinated team effort of a multidisciplinary group of dedicated health professionals, including physicians (surgical, medical, radiation, pediatric, gynecologic, neuro-oncologists), nurses, physicists, therapists, social workers, psychologists, physiatrists, medical support workers, support organizations.

Although there is general agreement about methods and applications of curative treatment for many cancers, there is less agreement about proper palliative treatment. Each specific clinical problem, in the perspective of uncontrollable cancer, may be different than any previously encountered. The integration of treatment options, with attention to possible sequelae, inconvenience, expense, and impact on the patient and family, usually requires greater physician judgment than required for decisions about curative treatment.

Communication between members of the health care team and the patient and family is essential. This requires: an honest relationship; attention to signals from the patient about information desired; explanations of the disease status, treatment aims and possible side effects; and a realistic fostering of hope that treatment can improve the patient’s quality of life, independent of length of survival.

Assessment of the accomplishments of palliative treatment may be more difficult than it is for curative treatment where tumor-free survival can be measured. Much of this evaluation is subjective. However, scales for pain assessment recently have been developed. Partial or temporary relief of problems such as cessation of bleeding or cough may be very satisfying to both the patient and physician. Treatment to prevent possible serious problems such as fracture through a metastasis-weakened weight-bearing bone is impossible to assess.

Obstacles to optimum palliative treatment include: lack of education and interest on the part of physicians, medical students, nurses, support personnel and families; cultural factors such as unrealistic fear of addiction to analgesic medications or unwarranted shielding of the patient from the diagnosis of cancer; and inadequate reimbursement, often secondary to unfortunate regulations. Expenses and contributions of family and medical personnel often are greater for palliative than for curative treatment.

Research opportunities related to palliative care of the patient with cancer are unlimited. It is gratifying that there has been a recent increase in interest.

Although the integration of many skills and methods are required for adequate palliative management of the patient with cancer, this book will emphasize the many potentially significant contributions of the proper medical use of ionizing radiations.

Indications for palliative radiation therapy for the patient with incurable cancer include: relief of pain; maintenance of skeletal integrity; control of bleeding; relief of obstruction; prevention of fistula formation; promotion of healing of surface lesions; relief of neurologic deficits; restraint of tumor growth; relief of systemic symptoms; restoration/preservation of function and cosmesis [2–4].

Palliative radiation therapy rarely requires complicated treatment planning. Plans should be simple, conservative, easily applicable, and reproducible. Treatment ports need to be carefully documented because additional irradiation at a later date may be required to an adjacent anatomical site. Treatment schedules need to correlate the best relief of symptoms and/or signs for the longest possible time with the least acute treatment-induced side effects. Such treatment should be delivered in the shortest reasonable overall time with minimal inconvenience and expense to the patient.

References

1.

Landis SH, Murray T, Bolden S, Wingo PA (1998) Cancer statistics, 1998. CA Cancer J Clin 48:6–30

2.

Janjan NA (2000) Palliative therapy: introduction. Semin Radiat Oncol 3:169–174

3.

Parker RG (1964) Palliative radiation therapy. JAMA 190: 1000–1002

4.

Parker RG (1996) Palliative use of ionizing radiations. Acta Oncol 8:981–987

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Chapter 2

Management of Pain

Robert G. Parker MD¹, Nora A. Janjan MD² and Michael T. Selch MD¹

(1)

Department of Radiation Oncology, UCLA School of Medicine, University of California, Los Angeles, 200 UCLA Medical Plaza, Suite B265, 90095–6951, Los Angeles, CA, USA

(2)

Department of Radiation Oncology, M.D. Anderson Cancer Center, 77030, 1515 Holcombe Boulevard, Houston, TX, USA

Pleasure is oft a visitant; but pain clings cruelly to us

John Keats, 1818

CONTENTS

2.1 Description of Pain

2.2 Assessment of Pain

2.3 Management

2.4 Anesthesia Approaches

2.5 Neurosurgical Approaches

2.6 Physical Medicine Approaches

2.7 Specific Contributions of Radiation Therapy

2.8 Psychological Support

2.9 Barriers to the Management of Cancer Pain

2.10 Economics of Cancer Pain Management

2.11 Compendium

References

Pain has been defined as an unpleasant sensory emotional experience associated with actual or potential tissue damage [1, 2]. Pain is subjective and every patient has his/her own interpretation. Fear of pain is a major component of patients’ attitudes towards cancer.

In an Eastern Cooperative Oncology Group (ECOG) study of 1308 outpatients being treated for cancer, 67 % reported having pain. In 36 %, this pain resulted in impaired function [3]. The pain was constant in 31 %. For 90 % of the patients, the pain was at least at a moderate level 25 % of the time. In another report of 1100 patients admitted to the M.D. Anderson Cancer Center [4], pain was a major symptom in 73 %. The pain was severe for 50 % of patients with metastases to bone, for 68 % of patients with cancer of the cervix, for 52 % of those with cancer of the prostate, and for 49 % of patients with cancer of the colon. In another study [5], pain restricted function in 55 % and interfered with sleep in 60 %.

The frequency and severity of pain also is related to the extent of the cancer. At the time of diagnoses, 30 %–45 % of patients experienced moderate to severe pain. This increased to 75 % of those with advanced cancer [6].

The World Health Organization (WHO) estimated that as many as 4 million people throughout the world may suffer from cancer-related pain [7, 8]. Consequently, the WHO has supported a worldwide cancer pain relief program.

Although pain can be controlled in about 90 % of patients with cancer using simple, easily available means [6, 9], this is not always accomplished. Unfortunately, as noted in a consensus statement from a 1990 National Cancer Institute Workshop [10], the undertreatment of pain and other symptoms of cancer is a serious and neglected public health problem ... every patient with cancer should have the expectation of pain control as an integral aspect of his/her care throughout the course of the disease.

There are many reasons why health care professionals undertreat pain: inability to evaluate and diagnose the etiology of pain; failure to understand the potential consequences of uncontrolled pain; inadequate communication with the patient; unfamiliarity with the many available methods of pain management such as radiation therapy, neurosurgical and anesthetic procedures, physical medicine; lack of experience using analgesic medications; fear of addiction.

Undertreatment of pain is more frequent in children, the elderly, females, those with low cognitive performance, those with language and cultural barriers, those who are economically disadvantaged [11].

Pain control in the patient with cancer is important for several reasons. Unrelieved pain causes tremendous suffering with consequent restriction of activity, lessening of appetite with resultant weight loss, interference with sleep, and consequent general deterioration of the patient’s quality of life. Unrelieved pain has serious psychological effects with an accentuated fear of death, disability and loss of personal control of life. Unrelieved pain can interfere with the patient’s acceptance of and compliance with treatment programs [6].

2.1 Description of Pain

There are three general types of pain:

1.

Somatic — secondary to the stimulation of nociceptors in cutaneous or deep tissues with consequent dull aching, but well-localized pain such as found in metastases to bone

2.

Visceral — resulting from the activation of noci ceptors in viscera with the production of a poorly localized, deep, squeezing, pressure sensation, such as noted in pancreatic cancer

3.

Neuropathic — following injury to or irritation of the peripheral or central nervous system with a burning, vice-like sensation such as found with involvement of the brachial plexus by cancer [9]

These three types of pain may be concurrent in a single patient, although neuropathic pain is less frequent (15 %–20 % of patients) [9].

2.2 Assessment of Pain

It is important in evaluating pain that the patient is believed by the health care providers, relatives, and friends. There is no place for a placebo treatment, for when such use is recognized by the patient, necessary trust of the physician is destroyed.

An adequate assessment of a patient’s pain includes a thorough general and pain-specific history and a thorough physical examination with extensive neurologic evaluation. A pain-specific history should include assessment of the intensity and character of the pain, with a description of onset, pattern, anatomic site, factors which aggravate or relieve, effects on physical-emotional-social function and success or failure of previous treatment [6]. This initial assessment should be followed by periodic, ongoing evaluations, particularly if there has been any change in the pain.

When treated as an outpatient, it is helpful if the patient keeps a pain diary.

There are several tools to assess the intensity of pain. For the numerical rating scale, the patient is asked to rate his/her pain from zero (no pain) to 10 (the worst pain imaginable). The visual analogue scale is a straight line ranging from no pain on the left end to worst pain on the right end. The patient is asked to mark on the line what they think their level of pain is. The categorical pain scale has four categories — none (0), mild (1–3), moderate (4–6) and severe (7–10) for the patient to select from. The pain faces scale uses six faces with varying expressions to represent levels of pain. This scale is useful for youngsters (Fig. 2.1). Pain at level 5 or over using the numerical rating or visual analogue scales usually results in functional impairment [3].

Fig. 2.1.

Pain assessment scales [14]

The American Pain Society Quality of Care Committee has advocated that pain measurement should be an integral part of patient care and quality improvement programs [12]. The following actions should be included:

1.

Make a report of unrelieved pain evident to the clinician.

2.

Make information about analgesics convenient where and when patient orders are written.

3.

Provide patients responsive and effective analgesic use.

4.

Request communication with the patient about his/her pain.

5.

Implement policies for the use of modern analgesic technologies.

6.

Record data about the patient’s pain in a prominent location in the chart as a fifth vital sign.

Pain management requirements have been listed by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in their hospital accreditation standards [13]. It was stated that patients have the right to appropriate assessment and management of pain including initial assessment and regular reassessment of pain; education of all relevant providers; education of themselves and families regarding their roles and the potential limitations and side effects of treatment; recognition of personal, cultural, spiritual, and ethnic beliefs. Patients are to be taught that pain management is part of their overall treatment.

Although most pain in patients with cancer is secondary to tumor, it can be iatrogenic, secondary to diagnostic procedures and treatment. Radiation therapy can produce severe discomfort such as that which arises from mucositis in the oral cavity, pharynx, or esophagus, desquamation and ulceration of the skin, or perianal skin reactions. Occasionally the irradiated tumor can become tender or painful soon after the initial treatment, presumably secondary to transient edema. Chemotherapy may produce mucositis and peripheral neuropathy. Surgical incisions from thoracotomy or abdominal perineal resection may cause acute or even chronic pain.

2.3 Management

Effective management of cancer-related pain should be based on treatment of the cancer if it is the underlying cause of the pain. In many circumstances, such as when the pain is secondary to metastases to bone, antineoplastic therapy should be the primary component of the pain management program. However, until tumor-related pain is relieved by antineoplastic therapy, it should be controlled by analgesics.

Therefore, oncologists must have a comprehensive knowledge of analgesics and other pain-relieving methods such as regional anesthesia, neurosurgical procedures, physical medicine and behavioral interventions. Pain management requires individualization for each patient and is best accomplished by a multidisciplinary group of health care personnel.

Analgesic drugs are the mainstay of the treatment of pain in the patient with cancer. The aim of treatment is adequate pain relief quickly achieved and maintained, using safe, convenient, readily available and easy to use medications. In addition to pain relief, the patient’s mental and physical function must be considered.

Guidelines for the use of analgesic drugs have been suggested by Foley [9].

1.

Use specific drugs for specific problems.

2.

Know the pharmacology of each drug, including potency, rapidity, and duration of action, kinetics, doses, side effects, cross-drug reactions.

3.

Administer the drugs on a regular schedule.

4.

Use the easiest effective route of administration, correlated with the patient’s needs and wishes.

5.

Use combinations of drugs to maximize effectiveness and minimize side effects.

6.

Anticipate and avoid or effectively treat druginduced side effects.

7.

Anticipate and prevent withdrawal symptoms, but if these occur, treat them vigorously.

8.

Anticipate and prevent complications, but if these occur treat them effectively.

It is better for a physician to be thoroughly familiar with and use a limited number of drugs than attempt to use a broad spectrum of less familiar medications. It often is useful to use a combination of drugs. In this circumstance, it is important to monitor the combined toxicities. When a drug is discontinued, a schedule of dose reduction (tapering) must be used.

Analgesic drugs can be classified into three categories. Each group of these drugs has specific indications, contraindications, limitations and side effects.

1.

Non-opioid analgesics, including aspirin, salicylate salts, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil), may control pain initially in 20 %–40 % of patients [9]. These drugs may be antipyretic and anti-inflammatory as well as analgesic and so are effective as adjuvants. They have a ceiling effect (i.e., 900–1300 mg doses of aspirin) after which further increases of dose do not increase the effectiveness. Tolerance and/or physical dependence are not produced. Side effects include hypersensitivity, hematologic changes, such as NSAID-induced inhibition of platelet aggregation, gastrointestinal complications, such as gastric bleeding after high doses of aspirin, and NSAID-induced renal or hepatic damage.

These drugs may be effective in relieving bone pain, but often are ineffective in relieving neuropathic pain.

2.

Opioid drugs can be divided into agonist (capable of combining with a receptor and initiating a reaction) and agonist-antagonist (capable of opposing the effects of another drug) classes. Nearly all drugs used for the relief of cancer pain are agonists (morphine, hydromorphone, oxycodone, oxymorphone, heroin, methadone, levorphanol, fentanyl, codeine, propoxyphene, hydrocodone). Operationally, agonist opioid drugs may be divided into weak, i.e., codeine, oxycodone combinations, and strong, i.e, morphine, hydromorphone. The definition of weak is not pharmacologic, but is based on the relatively high side-effect profile as doses are increased to treat severe pain [6]. These drugs, when given in pure form, do not have a ceiling effect inasmuch as the increase in analgesics is linearly related to increased dose [9]. However, when other analgesics are combined with aspirin or acetaminophen, there may be a functional ceiling effect due to toxicity.

3.

Adjuvant drugs can be used to enhance the analgesic effects of opioid drugs or they may be effective themselves in the treatment of specific types of pain, such as neuropathic or bone pain [14, 15]. These drugs include tricyclic antidepressants, such as amitriptyline, anticonvulsants, such as phenytoin, oral local anesthetics, such as mexiletine, cutaneous local anesthetics, such as 5 %–10 % lidocaine, and corticosteroids [9] as well as NSAIDS.

The World Health Organization (WHO) proposed the use of a three-step analgesic ladder to guide the selection of drugs [8, 16]. Pain was classified as mild, moderate, or severe.

A suggested algorithm for analgesic use is:

1.

If the pain is mild, start with a low-moderate dose of a non-opioid such as acetaminophen 600 mg every 4–6 h.

2.

If the pain increases from mild to moderate, increase the dose of the non-opioid, such as acetaminophen, to 6000 mg per day and add an adjuvant drug.

3.

If the maximum doses of non-opioid and adjuvant are not effective, start a low to medium dose of a so-called weak opioid such as codeine 20–60 mg every 4–6 h orally or an oxycodone combination plus a non-opioid drug.

4.

If the maximum dose of a weak opioid drug plus a non-opioid drug is ineffective, use a strong opioid, such as morphine 20–60 mg every 4–6 h and add a non-opioid and/or an adjuvant drug as needed. For patients with severe pain, a long-lasting drug such as fentanyl should be preceded by a titrated dose of a short-acting opioid.

Treatment guidelines for patients with cancer-related pain also have been developed by the National Comprehensive Cancer Network (NCCN) [14]. The decision trees are based on how bad the patient judges the pain to be. Initially, the patient is asked to rate their pain (see Fig. 1). An immediate goal is to determine whether the pain stems from a cancer-related emergency such as intestinal obstruction/perforation, metastases to the brain or meninges with consequent neurologic problems, spinal cord compression, or fracture through a metastasis to bone, which requires immediate treatment. If not an emergency, a treatment plan can be formulated and instituted. If the pain is rated 7–10, a short-acting opioid can be given and the dose incrementally increased. With all opioid administration, a program to combat constipation should be started concurrently. Antinausea drugs may be indicated. If the pain rating is 4–6, a short-acting opioid can be used immediately, followed by dose adjustment. If the pain rating is 1–3, an NSAID or short-acting opioid may be used. The response of the pain to the treatment needs to be continually assessed. If the pain rated 4–10 continues with inadequate response to opioids, nonmedical treatments should be considered. If pain rated 1–3 continues, other medications should be tried, often using sustained-released agents with breakthrough medication made available.

The frequency and timing of pain is important in the prescription of analgesics. If the pain is predictably related to function, such as a scheduled procedure or a regular bowel movement, an Oralet or short-acting analgesic may be adequate.

If the pain is constant, the titration of long-acting analgesics may be easier with a sustained release medication, such as MS contin or OxyContin. When the pain is controlled by a stable dose of a sustained release medication, fentanyl patches in equivalent doses can be substituted with changes only every 48–72 h.

It is important that for every patient the initially used analgesic and dose be appropriate for the pain level. Each patient should not go through the steps of the pain ladder to reach the proper level of pain medication. All analgesic programs need to be continually reassessed, initially every 24 h, and altered as necessary. Every patient has the right to be without pain.

Analgesic drugs are most effective when used on a regular schedule. For so-called breakthrough pain between the regular scheduled doses, additional doses of 5 %–15 % of the total daily dose of the same drug or another short-acting drug such as morphine or hydromorphone can be prescribed. The analgesic required should be adjusted to the individual patient’s needs [17]. In an evaluation of 100 inpatients, there were 182 changes in the analgesic drug or its route of administration, or both [18]. Even after pain control was achieved, 31 % of the regimes were changed to improve convenience of administration, 25 % were changed to reduce side effects, and 19 % were changed to reduce the invasiveness of administration. Pain management should be an ongoing process responding to changes in the patient’s needs [17].

The physician using analgesic drugs must be familiar with the side effects, possible untoward reactions, pharmacologic variations, alternate routes of administration, and relative costs.

Constipation usually results when opioid drugs are used. Therefore, it is important to alert the patient and start a prophylactic regime using stool softeners, a weak bowel stimulant, such as Senokot, and high fluid intake.

Nausea and vomiting, although uncommon, is usually a short-term effect which can be controlled by antiemetic drugs. If the nausea persists, another analgesic should be tried.

If the patient is unduly sedated by adequate doses of analgesics, a stimulant such as an amphetamine or Ritalin (20–30 mg in divided doses daily) may be helpful. Respiratory depression is rare.

Meperidine should not used because of its short-term duration of analgesia and long duration of toxic metabolites, which can cause multifocal clonus and seizures [9].

Tolerance to analgesic drugs is characterized by the need for increasing doses of an opioid to maintain the same level of pain relief. It is important to titrate the increasing doses until pain relief is achieved.

Prior to dose escalation, it is important to determine whether the increased pain is secondary to advancing cancer. If dose escalation is necessary, it may be useful to change to a different opioid, adding one-half of an equianalgesic dose of the original drug or adding an adjuvant drug to the original opioid.

Dependence on an opioid drug may be physical and/or psychological. Abrupt withdrawal may precipitate an abstinence syndrome [6]. Therefore, like steroids, a dose-tapering schedule must be used prior to discontinuation of the opioid.

Addiction is a behavioral or psychological pattern of action which is characterized by:

1.

Compulsive use of an opioid drug

2.

Loss of control over the use of the drug

3.

Continued use of the drug despite self harm [6].

It has been documented that the patient with cancer is unlikely to become addicted [19, 20]. Therefore, it is imperative that fear of addiction not interfere with the adequate use of opioid drugs to relieve cancer-related pain [21, 22]. This must be emphasized to the patients, their families, and medical care givers [23].

Drug elimination half-lives are important in the use of opioid drugs. Several half-lives of administered drugs may be needed to reach steady-state plasma levels [6]. These half-lives vary widely from 2–3 h for immediate release morphine to up to 50 h for methadone. For sustained release preparations such as morphine or oxycodone, dosing patterns of 8–12 h are necessary. Fentanyl, delivered as a transdermal patch, can be changed every 48–72 h.

The route of drug administration should be the simplest and least invasive necessary to produce adequate anesthesia. The oral route is the simplest and most frequently used. When given orally, opioids have a later onset of action and a longer duration than when given parenterally. Parenteral routes include intramuscular, subcutaneous, intravenous, epidural, and intrathecal. However, parenteral routes should not be used for repeated injections every few hours because of the risk of hematoma and infection.

Opioids, such as fentanyl, may be delivered continuously transdermally. A few drugs such as fentanyl and methadone may be absorbed through the oral mucosa and may be particularly useful for the treatment of breakthrough pain. Oxymorphone, hydromorphone, and morphine are available as suppositories. Over a long period, patients may benefit from the use of more than a single route of administration.

Usual doses for adults and indices of equivalency for the most frequently used medications are listed in Tables 2.1–2.6. Guidelines for using analgesics are repeated in Table 2.7. In prescribing these drugs, it important to know the prices, which may vary for equianalgesic doses of various medications and may vary amongst local retail suppliers.

Table 2.1.

Nonnarcotic analgesics (nonsteroidal anti-inflammatory drugs)

Table 2.2.

Narcotic agonist and antagonist drugs

a Morphine can be given as an immediate release formulation or as a sustained-release preparation (MS-Contin, Roxanol-SR)

Table 2.3.

Adjuvant analgesic drugs

Table 2.4.

Narcotic equivalency index

a One tablet of Percocet, Percodan, Tylox contains 5 mg of oxycodone

Table 2.5.

Drugs not recommended for cancer pain

Table 2.6.

Other useful drugs

Table 2.7.

Guidelines for using analgesics

2.4 Anesthesia Approaches

Although adherence to standard guidelines for the treatment of cancer pain (WHO [8, 17], NCCN/ACS [14]) results in adequate analgesia for 90 % of patients [24], interventional approaches are available and have been proposed as a fourth step in the WHO ladder [25]. Included are nerve blocks, spinal administration of local anesthetics and opioids, spinal cord stimulation, and surgical interventions.

Peripheral nerve blocks can be used diagnostically to identify the site of origin of pain as well as to treat pain. If a nerve block with a temporary anesthetic agent is successful, long-standing relief can be obtained using a neurolytic agent such as alcohol or phenol [26–28]. It is important that these anesthetic blocks not interfere with important body functions.

The sympathic nerve chain carries much nociceptive information, so blockade may relieve visceral as well as sympathetic pain [25]. Injection of the cervicothoracic (stellate) ganglion may treat ipsilateral facial, postmastectomy, and superior sulcus pain. Blockade of the celiac plexus may control abdominal, particularly pancreatic-induced, pain [29]. Pelvic pain may be relieved by a superior hypogastric ganglion block [30, 31].

Opioids, local anesthetics, spasmolytics and alpha-2 agonists (i.e., clonidine) have been introduced through epidural and subarachnoid routes [25]. Longterm drug administration may be accomplished by the use of external pumps with reservoirs [32].

Neuropathic pain, such as that seen after thoracotomy or extensive pelvic surgery as well as postherpetic neuralgia, may respond to electrical spinal cord stimulation [24, 33].

However, prior to the use of these more aggressive (invasive) treatments, noninvasive procedures must have been adequately tried and proved inadequate. Invasive procedures are required in less than 15 % of patients with cancer-related pain [34].

2.5 Neurosurgical Approaches

Palliative neurosurgery includes resection of tumor and/or specific pain-relieving procedures.

Decompression of a tumor-threatened spinal cord, removal of intracranial tumors, including metastases, for relief of increased intracranial pressure or threatened cranial nerves, and stabilization of vertebrae invaded by tumor are direct treatments of cancer [35–371.

Direct pain-relieving procedures may be neuroablative or neurostimulatory [37].

Neuroablative procedures produce a lesion along a nociceptive pathway and should be limited to patients with localized pain. Methods that have been used include cordotomy (interruption of the ascending neurospinothalamic pathway); rhizotomy (sectioning of the posterior roots); myelotomy (interruption of the crossing interneuronal fibers) [9]. Cordotomy, which may be performed percutaneously or openly, is optimally used for patients with well-localized unilateral pain who have a short life expectancy because the pain relief may be replaced by dysesthesias after 1–3 years [37].

Rhizotomy may produce a well-localized (specific dermatome) relief of pain through sectioning posterior sensory nerve roots [9]. This procedure has been used to relieve chest wall [38] and head and neck pain [39].

Midline myelotomy has been tried for patients with midline perineal or pelvic pain [40].

Stereotactic MRI-directed radiofrequency cingulotomy has been used for diffuse pain from widespread metastatic cancer [41].

Neurostimulating procedures, which produce anesthesia by stimulating afferent nerve pathways, include transcutaneous and percutaneous stimulation of peripheral nerves, spinal cord, or thalamus [42]. Transcutaneous electrical nerve stimulation (TENS) has been effective in the relief of neuropathic pain. Dorsal column stimulation has been used to relieve brachial or lumbosacral plexopathy [9]. Thalamic stimulation may relieve neuropathic pain from CNS lesions [43].

Acupuncture has been used for centuries by the Chinese. Acupuncture points are stimulated manually or electrically. Many anecdotal reports over many years support claims that this safe procedure may be effective in treating pain (J.J. Bonica 1970, personal communication), [44].

2.6 Physical Medicine Approaches

Physical medicine and rehabilitation programs have been underused in the treatment of the patient with cancer-related pain (J. Lehman 1970, personal communication). Easily available methods include diathermy (ultrasound, surface heating devices, hydrotherapy), transcutaneous electrical nerve stimulation (TENS), specific exercise programs, and selective immobilization [45].

Support devices, such as braces and mobile walkers, allow the patient to be mobile and they reduce the stress on bones at risk for pathologic fracture through tumor-involved bone. Massage, diathermy, and limited exercise programs may maintain muscle tonus and flexibility.

These procedures usually are adjuvants that increase the effectiveness of other treatments.

2.7 Specific Contributions of Radiation Therapy

Local-regional radiation therapy can effectively relieve pain caused by the involvement of an anatomic structure/organ by cancer. This and other antitumor therapies should be the primary treatment for pain relief whenever life expectancy is long enough for tumor regression and the maintenance of functional integrity is a concern.

Radiation therapy has been the mainstay of the treatment of patients with pain secondary to metastases to bone (see Chap. 3, Metastases to Bone). Relief can be achieved regardless of the primary tumor type, although the most frequent clinical experience has been with breast, prostate, and lung cancers. In addition to a high order of pain relief, structural integrity of bone may be maintained. Local-regional external beam irradiation should be delivered in as short a course as reasonable. Although multifraction-ated regimes carried to high total doses (i.e., 4000 cGy) have been reported to result in more frequent, complete, and prolonged pain relief [46], a range of doses, 29 Gy in 5 fractions, 30 Gy in 10 fractions, 35 Gy in 14 fractions and 8 Gy in a single fraction has been considered effective [47]. Although modest relapse rates have been noted [48], the median duration of pain relief has been reported to be 75 % of the median survival [49]. Retreatment is more likely following lower doses. Reirradiation of the lumbar or thoracic spine to doses of 20 Gy in 10 fractions after 30 Gy in 10 fractions has been considered probably appropriate under certain circumstances [46].

If pain-producing metastases to bone become widespread, local irradiation becomes impractical. In this circumstance, treatment of multiple lesions can be accomplished with hemibody irradiation or the administration of bone-seeking radioactive isotopes.

Initially half-body irradiation was delivered in single doses of 800 cGy to the lower body and 600 cGy to the upper body [50]. Partial pain relief was noted in about 75 % and complete pain relief was accomplished in 20 % of patients. Half of the patients noted pain relief within 48 h and 80 % reported pain relief within 1 week [50]. Single-dose programs have been replaced by the use of 3600 cGy delivered over 5 weeks [51] and 2500–3000 cGy divided into 9–10 fractions [52]. In all situations, preirradiation medications to prevent nausea must be used.

Radionuclides, which selectively localize to bone, have been used to treat widespread metastases for about 50 years [53]. All radionuclides used, except phosphorus-32, preferentially concentrate in new bone formation [54]. Consequently, those lesions likely to be responsive have an osteoblastic component. The most extensive experience has been with strontium-89, an elemental bone-seeker. Samarium-153, a bone-seeking ligand, has been increasingly used recently. The biological T1/2 of strontium-89 in bony lesions is about 6 weeks [55]. Treatment can be repeated after hematopoietic recovery, which usually occurs in about 3 months. Overall partial or complete pain relief has been reported for 81 % of patients with prostate cancer and 82 % of patients with breast cancer measured over 3 months [56].

Radiation therapy may be the best option for the relief of neuropathic pain caused by the infiltration or compression of nerves by cancer [18]. Radiation oncologists are likely to encounter patients who have localized pain secondary to superior sulcus (Pan-coast) tumors, brachial plexopathy associated with breast cancer, or epidural metastases. In treatment of these sites, the tolerance of the CNS and brachial plexus is dose-limiting. Therefore, a well-protracted course, such as 180–200 cGy daily to a total dose of 4500–5000 cGy is indicated.

Other less frequent pain problems often amenable to localized irradiation are perineal and low pelvic pain secondary to cancers of the rectum or prostate; pain in the upper right abdominal quadrant secondary to tumor-involvement of the liver capsule; discomfort from an enlarged spleen in a patient with leukemia or lymphoma; pain and diplopia related to orbital metastases, usually from breast cancer. Post-mastectomy chest wall recurrence in a patient with breast cancer may cause local pain responsive to chest wall irradiation. The severe, debilitating pain from pancreatic cancer may respond to local irradiation. When pain is secondary to obstruction of a ureter from prostatic or bladder cancer or obstruction of the esophagus from a primary cancer, any response to radiation therapy is slow, at best.

2.8 Psychological Support

Psychological support should start for each patient when the diagnosis of cancer is established. Such support is particularly important for the incurable patient, especially when suffering from pain.

Both cognitive and behavioral techniques may be useful [57]. Cognitive techniques influence how patients interpret pain, while behavioral techniques develop coping skills [58].

These patients frequently are anxious and depressed. It has been estimated that approximately 25 % of all patients with cancer can be severely depressed. This may increase to 75 % of those with advanced, uncontrolled cancer. This depression can be associated with contemplated or attempted suicide [59].

These patients fear death and feel that their lives are hopeless and out of control.

2.9 Barriers to the Management of Cancer Pain

Implementation of existing knowledge and techniques would have great impact on the treatment of cancer-related pain [60]. Barriers to good cancer pain management are related to health practitioners, especially physicians, to patients themselves, to medical institutions, and to the health care system [61–63].

The lack of communication between the patient and his/her physician is a major barrier to adequate cancer pain management [17]. Most physicians have not been adequately trained in pain management [64]. In a study of approximately 900 ECOG physicians who managed patients with cancer, 76 % diagnosed and assessed pain poorly; 61 % of physicians were hesitant to prescribe analgesics or believed patients were reticent to take them; 86 % inadequately prescribed these drugs; 33 % would not prescribe opioids unless the patient had a life expectancy of less than 6 months [64]. Seventy-six percent of primary care physicians and 50 % of medical oncologists were reluctant to prescribe morphine because of the perceived risk of side effects and addiction. Patient attitudes can inhibit adequate pain management [11]. A belief that good patients do not complain, a fear of addiction, and concerns about side effects have been reported [65].

Physicians often have great concern about regulatory oversight [17]. Guidelines published by the World Health Organization (WHO) and the Agency for Health Care Policy and Research (AHCPR) provide protection from unreasonable regulatory scrutiny [17, 66–68]. Under the Federal Controlled Substance Act, there is no restriction on the prescription of opioids for the treatment of pain in the patient with cancer and it is recognized that such use does not result in addiction [67].

Lack of adequate reimbursement can be a limiting factor. Cancer pain management is time-consuming and expensive. The availability of medications often is restricted and long-time use may not be financially covered. Medicare has paid for inpatient but not for outpatient oral analgesics [68].

Therefore, it is imperative that appropriate education programs be directed to health caregivers, patients and their families, government agencies and society at large.

2.10 Economics of Cancer Pain Management

The evaluation of the costs of the treatment of pain in cancer patients is an increasingly complex process. In 1994, the Cancer Pain Panel of the Agency for Health Care Policy and Research (AHCPR) suggested a framework for cost analysis [69]. These costs are associated with oral medications, parenteral analgesics, spinal analgesics, personnel, surgical procedures, anesthetic procedures, radiation therapy, non-drug interventions, unrelieved pain, savings related to various care settings, morbidity, justification of services, reimbursement biases, indirect costs to families, legal risks.

Many of the increased costs of health care in general, and cancer specifically, are based on the costs of technology. Jennett [70] has proposed an evaluation of technology in pain management related to cost-effectiveness:

1.

Unnecessary — if a less expensive treatment is equally effective (must be considered over the long term)

2.

Unsuccessful — if the expensive technology is instituted shortly before the patient’s death

3.

Unsafe — if the potential for complications is greater than the potential for benefit

4.

Unkind — if the side effects are likely to be worse than the pain

5.

Unwise — if there is an unreasonable diversion of resources

The best cost-benefit ratio results from the use of the least expensive, most effective treatment [69].

Although many factors other than costs must be considered in the choice of analgesics, there is a wide cost range among equianalgesic drugs. There is evidence that clinicians often are not aware of the costs of the medications they prescribe [71]. However, it is the responsibility of oncologists to be aware of variations in prices. A 19-fold difference in prices among equianalgesic opioids and a 25-fold difference among NSAID drugs have been reported [69, 71].

The use of single opioids in adequate doses may be less expensive than the use of prepared drug combinations. Furthermore, such drug combinations may have untoward side effects.

Alternate routes of administration of analgesics usually are more costly than oral or parenteral use. Costs for procedures may include equipment, surgery, hospitalization and specialized personnel [72]. Some estimated costs are (N.A. Janjan 2001, personal communication):

1.

Implantation of an epidural catheter — about $3,500 hospital/professional charges plus weekly visits and home medications ($100–$1000/week)

2.

Implantation of an intrathecal pump — $25,000 hospital/professional charges plus refills ($150–$350) every 1–3 months

3.

Home PCA — home set-up fee $500 plus home visits, medications ($100–$1000/week)

Subcutaneous administration, which has been used more in Europe and Canada than in the United States, may be less expensive than the intravenous route [73].

Hospice care should be part of the continuum of care for patients with cancer. Two-thirds of hospice patients are over 65 years of age and over 80 % are cancer patients [74, 75]. Hospice care has the potential to reduce home care costs. For example, more hospice patients received their analgesic drugs orally than in other home care settings [76]. Unfortunately, there are many Medicare limits on hospice reimbursements.

Illogical reimbursement biases may increase costs. For example, the costs of parenteral analgesics may be reimbursed, while less expensive oral medications may not be [69].

Indirect costs to the families of cancer patients, such as lost wages, as well as out-of-pocket expenses, are a major, underestimated and inadequately studied component of cancer pain management [77]. If family labor is included, the costs of home care of patients may approach, or even exceed, the costs of nursing home care.

Those patients who are not insured or are underinsured may have little access to any method of pain management and so even minimal expenses may lead to noncompliance [78].

In contrast to several high-technology methods, the proper use of palliative radiation therapy may be cost-effective. In an evidence-based study by the Swedish Council on Technology Assessment in Health Care [79], it was documented that the use of radiation therapy resulted in significant savings compared to the exclusive use of pharmacologic pain control in the treatment of metastases to bone through reduction of a range of morbidities, such as pathologic fractures and paralysis from spinal cord compression.

2.11 Compendium

1.

Pain is one of the greatest fears of patients with cancer and should be a primary concern of oncologists.

2.

Although pain is experienced by 75 % of those patients with advanced cancer and can be controlled in about 90 % of patients by using simple, easily available means, undertreatment is a frequent and serious problem.

3.

Undertreatment of pain in the patient with cancer is based on inadequate knowledge of the pathophysiology, the clinical courses, and consequences and the necessity of adequate treatment of pain; inadequate communication between patients and health care professionals; unfamiliarity of physicians with modern, available, potentially effective treatment methods; lack of knowledge and experience in using analgesic medications; fears of addiction by patients, relatives, and health care professionals. This undertreatment is more frequent when there are barriers to communication (children, unfamiliar languages, low cognitive performances), economic inadequacies, and bureaucratic interference.

4.

The three types of pain, somatic, visceral, and neuropathic, may require different treatments.

5.

Acute pain may be better defined and treated than chronic pain, which often severely reduces the patient’s quality of life.

6.

Placebos should never be used.

7.

A patient’s pain should be evaluated for its intensity, character, onset, pattern, anatomic site, success of previous treatment, aggravating factors. This evaluation should be repeated periodically and recorded.

8.

The most effective relief of pain follows successful treatment of the cancer if it can be documented as the underlying cause.

9.

Oncologists are responsible for being aware of available methods of relieving pain. Each should be knowledgeable about the use of analgesic medications.

10.

Analgesic drugs include non-opioids, opioids, and adjuvants. Algorithms for use have been proposed by the World Health Organization (WHO) and the National Comprehensive Cancer Network-American Cancer Society (NCCN/ACS).

11.

It is important to distinguish between tolerance (a need for increasing doses of analgesic drugs to maintain the same level of pain relief), dependence (characterized by an abstinence syndrome following abrupt withdrawal of a drug), and addiction (a behavioral pattern characterized by compulsive use, loss of control over use, and continued use of drugs despite harm to self and others). However, it is unlikely that patients with pain related to cancer will become addicted.

12.

Anesthesiologists, neurosurgeons, physiatrists, and psychologists can make specific contributions to pain management.

13.

Substantial barriers to effective pain management persist: lack of communication between the patient and members of the health care team; hesitancy of physicians to prescribe adequate analgesics; patients’ attitudes such as reluctance to complain; concerns about regulatory oversight of physicians; inadequate reimbursement.

14.

Adequate pain management is expensive. Such costs can be reduced by effective initial management; use of less-expensive, but equally effective drugs; careful and controlled use of high-tech methods; use of special support services such as hospice care.

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